Trial to Investigate the Effect of Schistosoma Mansoni Infection on the Response to Vaccination With MVA85A in BCG-vaccinated African Adolescents (TB036)
A Phase II Open Label Trial to Investigate the Effect of Schistosoma Mansoni (Sm) Infection on the Immunogenicity of a Candidate TB Vaccine, MVA85A, in BCG-vaccinated African Adolescents
Mycobacterium tuberculosis (M. tb) is a pathogen with worldwide distribution which infects humans causing tuberculosis (TB), a transmissible disease resulting in very high mortality and morbidity; development of an effective vaccine is a global health priority.
Over a billion people worldwide are infected with one or more helminths. Helminths are parasitic worms, of which Schistosoma mansoni is one species. There is some evidence that helminth infection may affect a person's response to a vaccine. In this trial the investigators hope to investigate whether Schistosoma mansoni infection affects adolescents' responses to a candidate TB vaccine called MVA85A, as adolescents are a crucial target group for an effective TB vaccine.
調査の概要
研究の種類
入学 (実際)
段階
- フェーズ2
連絡先と場所
研究場所
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Entebbe、ウガンダ
- MRC/UVRI Uganda Research Unit on AIDS
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria
Participants must meet all of the following criteria to enter the trial:
- Healthy adolescents aged 12-17 years (both male and female)
- Resident in the study area for the duration of the study period
- Confirmation of prior vaccination with BCG not less than 6 months prior to projected study vaccination date (by visible BCG scar on examination or written documentation)
- No relevant findings in medical history or on physical examination
- Written informed consent by parent or guardian
- Written informed assent by subject
- Refrain from blood donation during the trial
- Agree to avoid pregnancy for the duration of the trial (female only)
- Able and willing (in the Investigator's opinion) to comply with all the study requirements
- Stool sample negative for S. mansoni (group 1) or positive for S. mansoni infection (group 2), based on the results of the Kato Katz stool analysis
- Willing to delay treatment for schistosomiasis for at least one month (group 2)
Exclusion Criteria
Participants may not enter the trial if ANY of the following apply:
- Clinical, radiological, or laboratory evidence of current active TB disease
- Laboratory evidence at screening of latent M. tb infection as indicated by a positive ELISPOT response to ESAT6 or CFP10 antigens
- Previous treatment for active or latent tuberculosis infection
- Shared a residence within one year prior to day 0 with an individual on anti-tuberculosis treatment or with culture or smear-positive pulmonary tuberculosis
- Received a TST within 90 days prior to day 0
- Clinically significant history of skin disorder, allergy, immunodeficiency (including HIV), cancer (except BCC or CIS), cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder and neurological illness, drug or alcohol abuse
- History of serious psychiatric condition or disorder
- Concurrent oral or systemic steroid medication or the concurrent use of other immunosuppressive agents within 2 months prior to enrolment
- History of anaphylaxis to vaccination or any allergy likely to be exacerbated by any component of the study vaccine, including eggs
- Any abnormality of screening blood or urine tests that is deemed to be clinically significant or that may compromise the safety of the volunteer in the study
- Positive HBsAg, HCV or HIV antibodies
- Use of an investigational medicinal product or non-registered drug, live vaccine, or medical device other than the study vaccine for 30 days prior to dosing with the study vaccine, or planned use during the study period
- Administration of immunoglobulins and/or any blood products within the three months preceding the planned trial vaccination date
- Female currently lactating, confirmed pregnancy or intention to become pregnant during the trial period
- Screening blood sample positive for malaria or Mansonella perstans by microscopy
- Schistosoma mansoni infection intensity greater than 2000 eggs per gram of stool
- Any of the three screening stool samples positive for any helminths on Kato Katz examinations or for S. mansoni or Strongyloides stercoralis by PCR (group 1); or any of the three screening stool samples positive for helminths other than S. mansoni on Kato Katz examinations or for Strongyloides stercoralis by PCR (group 2)
- Screening urine sample positive for S. mansoni infection (group 1)
- Any other significant disease, disorder, or finding, which, in the opinion of the Investigator, may either put the subject at risk or may influence the result of the trial or may affect the subject's ability to participate in the trial
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:防止
- 割り当て:非ランダム化
- 介入モデル:並列代入
- マスキング:なし(オープンラベル)
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的:Group 1
Group 1 (Schistosoma mansoni uninfected): 12-24 BCG-vaccinated volunteers with no helminth infection.
Single dose of 1x10^8pfu MVA85A intramuscular vaccination at D0.
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Single dose of 1x10^8pfu MVA85A intramuscular vaccination
他の名前:
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実験的:Group 2
Group 2 (Schistosoma mansoni infected): 12-24 BCG-vaccinated volunteers with helminth infection.
Single dose of 1x10^8pfu MVA85A intramuscular vaccination at D0.
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Single dose of 1x10^8pfu MVA85A intramuscular vaccination
他の名前:
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この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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T cell immunogenicity by gamma-interferon ELISPOT of Ag85A response.
時間枠:8 weeks
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To compare T cell immunogenicity in adolescents with and without S. mansoni infection.
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8 weeks
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Evaluation of cytokines in supernatant of stimulated cells using Luminex and flow cytometry of Ag85A response.
時間枠:8 weeks
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Effects of S. mansoni infection on other aspects of the immune response following MVA85A immunisation.
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8 weeks
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Actively and passively collected data on adverse events.
時間枠:8 weeks
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To assess the safety of MVA85A vaccination in BCG-vaccinated African adolescents aged 12-17 years.
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8 weeks
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協力者と研究者
スポンサー
捜査官
- 主任研究者:Alison Elliot、MRC/UVRI and LSHTM Uganda Research Unit
出版物と役立つリンク
一般刊行物
- Wajja A, Namutebi M, Apule B, Oduru G, Kiwanuka S, Akello M, Nassanga B, Kabagenyi J, Mpiima J, Vermaak S, Lawrie A, Satti I, Verweij J, Cose S, Levin J, Kaleebu P, Tukahebwa E, McShane H, Elliott AM. Lessons from the first clinical trial of a non-licensed vaccine among Ugandan adolescents: a phase II field trial of the tuberculosis candidate vaccine, MVA85A. Wellcome Open Res. 2018 Sep 19;3:121. doi: 10.12688/wellcomeopenres.14736.1. eCollection 2018.
- Wajja A, Kizito D, Nassanga B, Nalwoga A, Kabagenyi J, Kimuda S, Galiwango R, Mutonyi G, Vermaak S, Satti I, Verweij J, Tukahebwa E, Cose S, Levin J, Kaleebu P, Elliott AM, McShane H. The effect of current Schistosoma mansoni infection on the immunogenicity of a candidate TB vaccine, MVA85A, in BCG-vaccinated adolescents: An open-label trial. PLoS Negl Trop Dis. 2017 May 4;11(5):e0005440. doi: 10.1371/journal.pntd.0005440. eCollection 2017 May.
研究記録日
主要日程の研究
研究開始
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (見積もり)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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